Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy ...demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer.
A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis.
The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization revealed a discordance rate of 9.5 and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen.
In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.
Purpose
There are no robust data on hemoglobin (Hb), lactate dehydrogenase (LDH), and calcium variability for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated ...with vascular endothelial growth factor (VEGF)-targeted therapy. We aim to evaluate prognostic implications of Hb, LDH, and calcium variability and establish a novel risk stratification model in RCC patients receiving targeted therapies.
Methods
We retrospectively studied an unselected cohort of patients with mRCC, who were treated with tyrosine kinase inhibitors. We assessed LDH variability, Ca variability, and Hb variability with various methods using standard deviation and fluctuation across thresholds. Kaplan–Meier and log-rank analyses were employed on OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance.
Results
A total of 59 patients intermediate-risk group according to the Memorial Sloan-Kettering Cancer Center with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective single-center study conducted between February 2008 and December 2011. The mean Hb was 12.4 g/dl (min–max 9.1–15.2) throughout the study. Multivariable-adjusted Cox regression showed that patients in the consistently low-Hb group and patients in the low-amplitude and high-amplitude groups had a statistically significant increase in risk compared with patients who were consistently on target (HR 4.1; 95 % CI 1.3–12.9 and HR 2.9; 95 % CI 1.05–8.1 and HR 4.4; 95 % CI 1.7–11.1, respectively). On the other hand, the higher mean LDH (LDH more than 1 >upper limit of normal) was associated with OS. LDH variability and Ca variability were not associated with mortality.
Conclusions
In patients with mRCC treated with VEGF-targeted therapy, Hb variability and mean LDH level might be associated with OS. This should be investigated prospectively.
Summary
Aim
The aim of the present study was to evaluate the effect of crizotinib on visceral organs in an experimental rat model.
Methods
Eighteen Wistar albino rats were divided into three groups: ...experimental toxicity was induced with crizotinib (10 mg/kg) administered for 28 days (Group 1), 42 days (Group 2) orally by gavage. Control group received only distilled water. Rats in Group 1 and Group 2 were sacrificed after the collection of blood and tissue samples on the 28th and 42nd days, respectively.
Results
Subjects in Group 1 and Group 2 had abnormal histology mainly in lung and liver. There were intraalveolar hemorrhage in lungs; mild portal inflammation, perivenular focal and confluent necrosis in liver; inflammatory reaction in renal pelvis and periureteral areas, and focal pancreatitis in pancreas.
Conclusion
This study is the first to evaluate the histopathological features of toxicity of crizotinib in a rat model.
Surgical resection of asymptomatic primary colorectal cancer in patients presenting with synchronous unresectable metastatic disease is controversial. Concerns and controversies remain over combining ...cytotoxic chemotherapy with bevacizumab in this patient population.
We identified medical records of 99 patients with synchronous metastatic primary colorectal cancer who received chemotherapy with bevacizumab as their initial treatment. The incidence of subsequent use of surgery and surgical outcomes were recorded. Patients were also assessed for overall survival.
Patients who received bevacizumab-containing chemotherapy for synchronous metastatic primary colorectal cancer were divided into the non-surgery and surgery groups according to the resection status of their asymptomatic primary tumor. In the non-surgery group, two patients (4.4%) underwent additional surgery, while three patients (5.7%) required surgery for rectovesical fistula in the surgery group. The median overall survival was 17 months for the non-surgery group (95% CI: 10.6-23.3 months) and 23 months for the surgery group (95% CI: 21.3-24.6 months; P = 0.322).
This study utilizing chemotherapy with bevacizumab did not result in an increased rate of morbidity related to the unresected primary tumor. Survival is not compromised by leaving the primary colon tumor intact.
Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via ...the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey.
Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A).
A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting.
This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.
Objective
The objective of this retrospective study is to investigate the association between survival and maximum standardized uptake values (SUV
max
) of liver metastases detected by pre-treatment ...positron emission tomography-computed tomography (PET-CT) in patients with adenocarcinoma of unknown primary origin (ACUP).
Methods
A total of 58 patients with ACUP and liver metastases confirmed histopathologically by liver biopsy and pre-treatment PET-CT were included in this study. SUV
max
values of the liver lesions were measured and their association with survival was investigated.
Results
The median age was 62 years; 63.8 % of the patients were males and 36.2 % were females. The median overall survival was calculated as 10.7 months (OS). The median SUV
max
of the liver metastases was 8.6. Accordingly, two groups were established: one with values <8.6 and the other with ones ≥8.6. No differences were detected between the two groups with respect to general characteristics. Median OS was 13.2 months in the group with SUV
max
<8.6 compared to 7.4 months in the group with SUV
max
≥8.6. This difference was statistically significant (
p
= 0.033). SUV
max
(HR 1.104, 95 % CI 1.013–1.204,
p
= 0.025), age (HR 1.033, 95 % CI 1.002–1.064,
p
= 0.034), presence of chemotherapy (HR 2.296, 95 % CI 1.136–4.641,
p
= 0.021) and LDH level (HR 1.002, 95 % CI 1.001–1.003,
p
= 0.007) were identified as independent prognostic factors affecting survival in the multivariable analysis. This is the first report evaluating the impact of SUV
max
for liver metastases on ACUP patient survival.
Conclusion
The SUV
max
of liver metastases evaluated by PET-CT is a prognostic factor influencing survival of patients with ACUP.
Abstract Treatment of malignant gliomas has changed substantially over the last few years. An oral alkylating agent, temozolomide, has become the standard agent for glioma management. Although it is ...generally well tolerated, it can cause lymphopenia and may lead to opportunistic infections. We report on a patient with malignant glioma who developed opportunistic cytomegalovirus (CMV) pneumonia following the termination of temozolomide therapy. The patient was admitted with acute dyspnea, fever and hypoxia, and she was diagnosed with CMV pneumonitis using a PCR-based CMV-DNA analysis. After treatment with ganciclovir, she recovered dramatically. To our knowledge, although there have been reported cases of Pneumocystis carinii infection associated with temozolomide therapy, there has only been one other case of CMV infection. We also review this report.
Sister Mary Joseph’s periumbilical metastatic nodule is an ominous harbinger of an internal malignancy usually originating from gastrointestinal or genital system primary cancers. At the time of ...diagnosis, they are inoperable and therefore deemed incurable, suggesting an invariably dismal prognosis. Periumbilical neoplastic deposits from primary non-Hodgkin’s lymphoma are extremely rare. A 72-year-old white male with a history of gastric cancer was referred with a painful lesion in the umbilicus. A delayed biopsy of the nodule showed diffuse large B-cell lymphoma. After a work up, he was successfully treated with standard combination chemotherapy and achieved complete remission. However, the patient developed central nervous system relapse and died a few months later. Our patient illustrates the importance of obtaining a tissue diagnosis before diagnosing an internal carcinoma as the underlying cause in patients with Sister Mary Joseph’s nodule. We should keep in mind that not all periumbilical tumoral deposits are the same.
Systemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. This report ...describes the case of a 45-year-old man with advanced gastric cancer who developed severe ischemic colitis after chemotherapy with cisplatin and capecitabine. The patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea. He had a normal white blood cell count throughout his illness; the assay of stool specimens for
Clostridium difficile
toxins and the stool cultures were both negative. An endoscopy showed a mild, transient ischemic colitis. Although cisplatin is related to severe colonic cytotoxicity, it has not been previously reported that capecitabine induces arterial thrombosis and necrosis of the gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is the most frequent complication in patients with cancer who undergo capecitabine-based chemotherapy and develop gastrointestinal toxicity. Once
Clostridium difficile
infection has been excluded, a diagnosis of ischemic colitis should be considered, especially in patients with cancer who have normal white blood cell counts.
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